The pathogenesis, immunology, natural history and therapy of human herpesvirus infections are being investigated. Immunocompetent and immunodeficient patients, including those with AIDS, who possess a wide range of herpesvirus infections have been identified and studied. Our major emphases have been on frequently recurring genital herpes simplex virus infections and on chronic Epstein-Barr virus infection. During the past year we have completed a large longitudinal study of symptoms and virus shedding patterns in patients with frequently recurring genital herpes before, during and after suppressive acyclovir therapy. As part of that study we have identified and quantitated shedding of virus in the absence of symptoms. We have observed and studied an episode of transmission of genital herpes associated with an episode of asymptomatic shedding. In terms of chronic Epstein-Barr virus infection, we have continued long term observation of a series of patients with a chronic fatiguing illness associated with elevated Epstein-Barr virus antibody titers. We have initiated a placebo controlled trial of intravenous and high dose oral acyclovir therapy for patients with that disorder. During the coming year we plan to initiate another study of asymptomatic shedding in patients with genital herpes and to complete our current placebo controlled acyclovir trial for chronic EBV infections.